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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Grond, S; Radner, FPW; Eichmann, TO; Kolb, D; Grabner, GF; Wolinski, H; Gruber, R; Hofer, P; Heier, C; Schauer, S; Rülicke, T; Hoefler, G; Schmuth, M; Elias, PM; Lass, A; Zechner, R; Haemmerle, G.
Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation.
J Invest Dermatol. 2017; 137(2):403-413
Doi: 10.1016/j.jid.2016.09.025
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- Co-Autor*innen der Med Uni Graz
- Eichmann Thomas
- Grabner Gernot
- Hofer Peter
- Höfler Gerald
- Kolb Dagmar
- Schauer Silvia
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- Abstract:
- Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism.
- Find related publications in this database (using NLM MeSH Indexing)
- 1-Acylglycerol-3-Phosphate O-Acyltransferase - physiology
- Animals - administration & dosage
- Cell Differentiation - administration & dosage
- Ceramides - biosynthesis
- Keratinocytes - cytology
- Lipase - physiology
- Mice - administration & dosage
- Skin - embryology, metabolism
- Triglycerides - metabolism